Induction and termination of inflammatory signaling in group B streptococcal sepsis
Authors: Wennekamp, Julia1; Henneke, Philipp1
Source: Immunological Reviews, Volume 225, Number 1, October 2008 , pp. 114-127(14)
Publisher: Blackwell Publishing
Abstract:
Summary: Group B streptococcus (GBS) is part of the normal genital and gastrointestinal flora in healthy humans. However, GBS is a major cause of sepsis and meningitis in newborn infants in the Western world and an important pathogen in many developing countries. The dissection of the host response to GBS may increase the general understanding of innate immunity in sepsis, because newborn infants lack a sufficient adaptive response. Inflammatory signal induction in macrophages by GBS seems largely preserved in newborn infants, as shown both in vitro and in vivo. The engagement of Toll-like receptor 2 (TLR2) by lipoproteins and a myeloid differentiation factor 88 (MyD88)-dependent pathway induced by GBS cell wall are both important in this context. TLR2 activation of microglia by GBS induces neuronal damage, which might account for the high morbidity of GBS meningitis. At the same time, TLR2 mediates activation-induced cell death (AICD), a process involved in the containment of inflammation. In newborn infants, AICD and anti-bacterial polymorphonuclear leukocyte activity appears to be compromised. Accordingly, neonatal aberrations in the pathogen-specific negative control of inflammatory signaling are likely to contribute to excessive inflammation and neurological sequelae in GBS sepsis and meningitis.Keywords: monocytes/macrophages; bacterial infection; cytokines; Toll-like receptors; apoptosis/autophagy; cell activation
Document Type: Research article
DOI: 10.1111/j.1600-065X.2008.00673.x
Affiliations: 1: Centre for Pediatrics and Adolescent Medicine, University Medical Centre, Freiburg, Germany.

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